The effect of stress-deprivation and cyclic loading on the TIMP/MMP ratio in tendon cells: An in vitro experimental study
The effect of stress-deprivation and cyclic loading on the TIMP/MMP ratio in tendon cells: An in vitro experimental study
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DOI：
10.1080/09638280701785395
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发表时间：
2008-01-01
影响因子：
2.2
通讯作者：
Lavagnino, Michael
中科院分区：
文献类型：
--
作者：
Gardner, Keri;Arnoczky, Steven P.;Lavagnino, Michael
目的。目的：探讨应激剥夺和循环负荷对大鼠尾肌腱(RTT)细胞TIMP-1/MMP13基因表达的影响。方法。成年RTT在存在或不存在基质金属蛋白酶抑制剂(伊洛马特)的情况下进行0、24、48或72小时的应激剥夺，或在组织培养条件下接受1%、3%或6%应变24小时。用定量聚合酶链式反应检测TIMP-1和MMP13(大鼠间质胶原酶)的mRNA表达，计算TIMP/MMP值。结果。对照RTT组织中TIMP-1与MMP13的比值为3.73：10.73。应激剥夺24小时后，TIMP-1/MMP-13比值(0.25：10.04)显著降低，且随着应激剥夺时间的延长，TIMP-1/MMP-13的表达继续显著增加。与正常对照组相比，在应激剥夺的样本中，使用伊洛马特抑制基质金属蛋白酶-13mRNA的表达不会改变TIMP-1的表达。在所研究的所有应变水平，循环负荷显著增加TIMP-1/MMP-13的表达。结论。RTT通常具有TIMP-1/MMP-13的阳性表达比率。当循环负荷增加TIMP-1/MMP13比值时，细胞内平衡张力的丧失通过显著增加MMP13mRNA的表达而不是降低TIMP的表达来逆转该比值。负的TIMP/MMP值与肌腱病的发病机制有关。在这些患者中，通过运动提高TIMP/MMP值可能有助于肌腱病的治疗。
Purpose. To determine the effect of stress deprivation and cyclic loading on TIMP-1/MMP-13 mRNA expression ratio in rat tail tendon (RTT) cells. Method. Adult RTTs were stress-deprived for 0, 24, 48, or 72 hours in the presence or absence of a MMP inhibitor (ilomastat), or subjected to 1%, 3%, or 6% strain for 24h under tissue culture conditions. TIMP-1 and MMP-13 (rat interstitial collagenase) mRNA expression were measured using quantitative PCR and TIMP/MMP ratios were calculated for each group. Results. The ratio of TIMP-1 to MMP-13 in control RTTs was 3.73:10.73. Stress deprivation for 24h significantly decreased the TIMP-1/MMP-13 ratio (0.25:10.04) and MMP-13 expression continued to increase significantly with time of stress deprivation. Inhibition of MMP-13 mRNA expression with ilomastat in stress-deprived samples did not alter TIMP-1 expression when compared to normal controls. Cyclic loading significantly increased TIMP-1/MMP-13 expression at all strain levels examined. Conclusions. RTTs normally have a positive TIMP-1/MMP-13 expression ratio. While cyclic loading increased the TIMP-1/MMP-13 ratio, loss of cellular homeostatic tension inversed this ratio through a significant increase in MMP-13 mRNA expression rather than a decrease in TIMP expression. A negative TIMP/MMP ratio has been implicated in the pathogenesis of tendinopathy. Increasing the TIMP/MMP ratios in these patients through exercise may be beneficial in the management of tendinopathy.